This application is designed to provide Scott H. Sicherer, MD with a program of mentored, patient-oriented research that will facilitate his development as an independent physician scientist. Dr. Sicherer completed his residency and chief residency in pediatrics, his fellowship in allergy and immunology and he has been Assistant Professor of Pediatrics at Mount Sinai School of Medicine since July, 1997. During the latter portion of his fellowship training and as faculty, he has concentrated his research efforts on the clinical manifestations of food allergy, particularly peanut allergy. He has amassed clinical data on a large group of peanut-allergic patients including preliminary data to indicate a genetic influence on peanut allergy. This award would allow him the unique opportunity to acquire cross- training in genetics while pursuing a multidisciplinary, patient- oriented research project to dissect the genetic basis of peanut allergy. Allergy to peanut affects 0.6 percent of the general population, is responsible for the majority of severe, life-threatening food allergic reactions, and sensitivity is rarely outgrown. Because peanut is ubiquitous in the American diet, sensitization among susceptible individuals is the rule and accidental ingestions among allergic individuals is common. Despite the seriousness of the allergy, little is known about the genetic basis of this or any other food allergy. This proposal will test the hypothesis that peanut allergy is a complex genetic disease. Several approaches will be taken to test the hypothesis: 1) The heritability of peanut allergy will be determined by comparing the concordance rate of the allergy in mono- and dizygotic twin pairs; 2) Since HLA class II molecules are an attractive candidate as one determinant for peanut allergy, serotyping will be performed and genotype frequencies compared for evidence of association in families with affected probands; and 3) a genome- wide search will be performed on families with two affected siblings using highly polymorphic markers that systematically cover the entire genome and the data analyzed for linkage to major loci contributing to peanut allergy. Dr. Sicherer will be supported in his endeavors with protected research time, access to the General Clinical Research Center and institutional core facilities, and dedicated laboratory space. His development will be fostered by the serious committment of his mentors to guide him in the proposed studies and in the responsible conduct of research, and by the outstanding research and intellectual environment at Mount Sinai.